Method for diagnosing and/or predicting the development of an allergic disorder and agents for treating and/or preventing same

Abstract

The present invention relates to genes whose level of expression is different in allergic animals compared with non-allergic animals. In particular, the present invention relates to a method for predicting the development of an allergic disorder in a mammal by determining the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within a nucleic acid pool that have been predetermined to either increase or decrease in response to allergy.

1 . A method for predicting the development of an allergic disorder in a mammal comprising the steps of: (a) contacting a cell of the mammal with an allergen; (b) contacting a cell of a non-allergic mammal with the same allergen used in step (a); (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA; (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and (e) compare the expression patterns in step (d), wherein the difference in the levels of expression is predictive of whether the mammal in step (a) will develop allergy. 
   
   
       2 . A method for diagnosing an allergic disorder in a mammal comprising the steps of: (a) contacting a cell of the mammal with an allergen; (b) contacting a cell of a non-allergic mammal with the same allergen used in step (a); (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA; (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and (e) compare the expression patterns in step (d), wherein the difference in the levels of expression is diagnostic that the mammal in step (a) is allergic. 
   
   
       3 . A method according to  claim 1 , wherein the panel of specific sequences further comprises one or more of SLC37A3, PALM2-AKAP2, NSMCE1, TSPAN13, SYTL3, SFRS8, FIP1L1, MAML3, TRIM4, SIAH1, ITPR1, ITSN2, CLCF1, CRLF1, CLIC5, IGJ, NFKBIZ, DLC1, GBP5, PEG10, HOMER2, ZBTB8, MOBKL2C, EDG3, MELK, PHC3, TTC3, KLK1, KCNV2, IL1F9, GBP1, SEL1, IL1R2, IFI44L or LIX1L. 
   
   
       4 . A method according to  claim 1 , wherein the cell is a peripheral blood mononuclear cell (PBMC). 
   
   
       5 . A method for preventing or treating an allergic disorder in a mammal comprising the steps of:
 (a) obtaining a pool of nucleic acid molecules isolated from the mammal's organ, tissue or cell, wherein the nucleic acid is RNA or a cDNA copy of RNA;   (b) determining the gene expression pattern of a panel of specific sequences within the pool of nucleic acid molecules described in (a) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences and wherein said panel includes CAMK2D and CDH1;   (c) identify a gene expression pattern for one or more of the panel of specific sequences which is different when compared with the predetermined level of expression; and   (d) administering an agent capable of bringing the gene expression pattern to the predetermined level of expression.   
   
   
       6 . A method of selecting an agent for the treatment of a mammal having an allergic disorder, comprising:
 (a) contacting a cell of an allergic mammal with a test agent;   (b) contacting a cell of a non-allergic mammal with the same test agent used in step (a);   (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (e) compare the expression patterns in step (d), and if the levels of expression of said panel are similar then the test agent is useful in the treatment of a mammal with an allergy.   
   
   
       7 . A method of selecting a prophylactic agent for a mammal in which an allergic disorder is to be prevented, comprising:
 (a) contacting a cell of suspected allergic mammal with a test agent;   (b) contacting a cell of a non-allergic mammal with the same test agent used in step (a);   (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (e) compare the expression patterns in step (d), and if the levels of expression of said panel are similar then the test agent is useful as a prophylactic agent in the prevention of an allergy in the mammal.   
   
   
       8 . A control agent capable of modulating the expression of a gene associated with an allergic disorder:
 (a) contacting a cell of an allergic mammal with a test agent;   (b) contacting a cell of a non-allergic mammal with the same test agent used in step (a);   (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (e) compare the expression patterns in step (d), and if the levels of expression of said panel are different in the presence of the test agent this indicates that the agent is capable of modulating the expression of CAMK2D and CDH1.   
   
   
       9 . A method of monitoring a mammal during therapy for an allergic disorder, comprising:
 (a) contacting a cell of the mammal before therapy with an allergen;   (b) contacting a cell of the mammal under therapy with the same allergen used in step (a);   (c) contacting a cell of a non-allergic mammal with the same allergen used in step (a);   (d) obtaining a sample of nucleic acid isolated from the cells in steps (a), (b) and (c), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (e) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (d) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (f) compare the expression patterns in step (e) and determine whether the level of expression has changed during therapy,   wherein a change in the level of expression during therapy is an indication of the progress of the therapy.   
   
   
       10 . A method of determining the potential responsiveness of an animal suffering from an allergic disorder to treatment for the allergic disorder, comprising:
 (a) contacting a cell of an allergic mammal with an allergen;   (b) contacting a cell of a non-allergic mammal with the same allergen used in step (a);   (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (e) compare the expression patterns in step (d), wherein a difference in the levels of expression is indicative of the potential responsiveness of the animal to the therapy.   
   
   
       11 . A method of predicting the risk of an animal suffering from an allergic disorder progressing to a more severe and/or persistent form of the allergic disorder, comprising:
 (a) contacting a cell of an allergic mammal with an allergen;   (b) contacting a cell of a non-allergic mammal with the same allergen used in step (a);   (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (e) compare the expression patterns in step (d), wherein any difference in the level of expression between the allergic mammal and non-allergic mammal is predictive of the risk of the allergic mammal developing a more severe and/or persistent form of the allergic disorder.   
   
   
       12 . A method of determining the immunological phenotype of an allergic disorder in an animal, comprising:
 (a) contacting a cell of an allergic mammal with an allergen;   (b) contacting a cell of a non-allergic mammal with the same allergen used in step (a);   (c) obtaining a sample of nucleic acid isolated from the cells in steps (a) and (b), wherein the nucleic acid is RNA or a cDNA copy of RNA;   (d) determine the gene expression pattern of a panel of specific sequences comprising CAMK2D and CDH1 within each nucleic acid pool described in (c) that have been predetermined to either increase or decrease in response to allergy, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences; and   (e) compare the expression patterns in step (d), wherein the level of expression is indicative of the immunological phenotype of the animal.   
   
   
       13 . An isolated molecule comprising one or more of:
 a) the sequence of a nucleic acid selected from the group consisting of CAMK2D, CDH1, SLC37A3, PALM2-AKAP2, NSMCE1, TSPAN13, SYTL3, SFRS8, FIP1L1, MAML3, TRIM4, SIAH1, ITPR1, ITSN2, CLCF1, CRLF1, CLIC5, IGJ, NFKBIZ, DLC1, GBP5, PEG10, HOMER2, ZBTB8, MOBKL2C, EDG3, MELK, PHC3, TTC3, KLK1, KCNV2, IL1F9, GBP1, SEL1, IL1R2, IFI44L and LIX1L, or a biologically active fragment thereof;   b) an isolated nucleic acid molecule which is the complement of a sequence of a);   c) an isolated nucleic molecule which hybridises under stringent conditions to a nucleic acid molecule of a) or b); and/or   d) an isolated polypeptide encoded by a nucleic acid molecule of a), b) or c), for use in the treatment or prevention of an allergic disorder.   
   
   
       14 . A therapeutic or prophylactic agent, comprising one or more of:
 a) an isolated nucleic acid molecule having the sequence of a nucleic acid selected from the group consisting of CAMK2D, CDH1, SLC37A3, PALM2-AKAP2, NSMCE1, TSPAN13, SYTL3, SFRS8, FIP1L1, MAML3, TRIM4, SIAH1, ITPR1, ITSN2, CLCF1, CRLF1, CLIC5, IGJ, NFKBIZ, DLC1, GBP5, PEG10, HOMER2, ZBTB8, MOBKL2C, EDG3, MELK, PHC3, TTC3, KLK1, KCNV2, IL1F9, GBP1, SEL1, IL1R2, IFI44L and LIX1L, or a biologically active fragment thereof;   b) an isolated nucleic acid molecule which is the complement of a sequence of a);   c) an isolated nucleic molecule which hybridises under stringent conditions to a nucleic acid molecule of a) or b); and/or   d) an isolated polypeptide encoded by a nucleic acid molecule of a), b) or c), together with a pharmaceutically acceptable carrier.   
   
   
       15 . An agent according to  claim 15 , wherein the agent is for use in the treatment or prevention of an allergic disorder. 
   
   
       16 . A method of treating or preventing an allergic disorder, comprising the step of administering to a mammal one or more of:
 a) an isolated nucleic acid molecule having the sequence of a gene selected from the group consisting of CAMK2D, CDH1, SLC37A3, PALM2-AKAP2, NSMCE1, TSPAN13, SYTL3, SFRS8, FIP1L1, MAML3, TRIM4, SIAH1, ITPR1, ITSN2, CLCF1, CRLF1, CLIC5, IGJ, NFKBIZ, DLC1, GBP5, PEG10, HOMER2, ZBTB8, MOBKL2C, EDG3, MELK, PHC3, TTC3, KLK1, KCNV2, IL1F9, GBP1, SEL1, IL1R2, IFI44L and LIX1L, or a biologically active fragment thereof;   b) an isolated nucleic acid molecule which is the complement of a sequence of a);   c) an isolated nucleic molecule which hybridises under stringent conditions to a nucleic acid molecule of a) or b);   d) an isolated polypeptide encoded by a nucleic acid molecule of a), b) or c); and/or   e) an agent capable of modulating the expression of a molecule of a), b), and/or c), or which specifically binds a polypeptide of d).   
   
   
       17 . A method according to  claim 17 , wherein the agent is antisense to the nucleic acid sequence of a gene selected from the group consisting of CAMK2D, CDH1, SLC37A3, PALM2-AKAP2, NSMCE1, TSPAN13, SYTL3, SFRS8, FIP1L1, MAML3, TRIM4, SIAH1, ITPR1, ITSN2, CLCF1, CRLF1, CLIC5, IGJ, NFKBIZ, DLC1, GBP5, PEG10, HOMER2, ZBTB8, MOBKL2C, EDG3, MELK, PHC3, TTC3, KLK1, KCNV2, IL1F9, GBP1, SEL1, IL1R2, IFI44L and LIX1L, or a biologically active fragment thereof. 
   
   
       18 . A method according to  claim 2 , wherein the panel of specific sequences further comprises one or more of SLC37A3, PALM2-AKAP2, NSMCE1, TSPAN13, SYTL3, SFRS8, FIP1L1, MAML3, TRIM4, SIAH1, ITPR1, ITSN2, CLCF1, CRLF1, CLIC5, IGJ, NFKBIZ, DLC1, GBP5, PEG10, HOMER2, ZBTB8, MOBKL2C, EDG3, MELK, PHC3, TTC3, KLK1, KCNV2, IL1F9, GBP1, SEL1, IL1R2, IFI44L or LIX1L. 
   
   
       19 . A method according  claim 2 , wherein the cell is a peripheral blood mononuclear cell (PBMC).